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Chronic Fatigue Syndrome Advisory Committee (CFSAC)MeetingMay 16-17, 2007 Room 800, Hubert H. Humphrey Building Members in AttendanceCFS Advisory Committee Members Chair
Voting Members
Ex Officio Members Centers for Disease Control and Prevention (CDC) William C. Reeves, MD (Primary) CDR Drue H. Barrett, PhD (Alternate) Food and Drug Administration (FDA) Marc W. Cavaille-Coll, MD, PhD Health Resources and Services Administration (HRSA) Deborah Willis-Fillinger, MD (Primary) National Institutes of Health (NIH) Eleanor Hanna, PhD Social Security Administration (SSA) Laurence Desi, Sr., MD, MPH (Primary) James Julian, Esq. (Alternate) Executive Secretary (Designated Federal Officer) Anand K. Parekh, MD, MPH Invited Speakers Linda Milne, Organization for Fatigue and Fibromyalgia Education & Research (OFFER) Wednesday, May 16, 2007
Dr. Anand Parekh Dr. Parekh called the Chronic Fatigue Syndrome Advisory Committee (CFSAC) meeting to order and conducted a roll call of voting and ex officio members to establish a quorum. All members were present except Dr. Arthur Hartz, who was in transit. In his opening remarks, Dr. Parekh noted that CFSAC was chartered in 2002 to advise and make science-based recommendations to the Department of Health and Human Services (HHS) Assistant Secretary, currently John O. Agwunobi, MD, and Secretary, currently Michael O. Leavitt. Dr. Parekh welcomed new CFSAC members, greeted those who were returning as voting and ex officio members, and thanked Dr. James Oleske for agreeing to chair the committee. Dr. Parekh also acknowledged members of the public in attendance, outlined the two-day agenda, and discussed items provided in the meeting folders distributed to CFSAC members. These items included:
In response to a committee member's request, Dr. Parekh agreed to provide electronic copies of presentations, statements, and other meeting documents whenever possible. Dr. James Oleske Dr. Oleske recognized and thanked the five new CFSAC members [Dr. Hartz was in transit at the time of the introductions]:
Noting Dr. Snell's expertise in quality of life, Dr. Oleske asked all new members to consider on which of three CFSAC subcommittees they would like to serve-Research, Quality of Life, or Education. Dr. Oleske predicted that when subcommittee reports are given on meeting day two, members would recognize that while much has been accomplished, "we have an awful lot still to do." He said that the subcommittees can be productive in guiding CFSAC toward recommendations. CFSAC Community/Organizational UpdatesLinda Milne, Organization for Fatigue and Fibromyalgia Education & Research (OFFER) The motto of OFFER, which is headquartered in Salt Lake City, UT, reflects its purpose: Offer hope. Milne had been living with CFS for five years when she moved to Utah in 2001 and got referred to Dr. Bateman at the Fatigue Consultation Clinic in 2002. Her referral coincided with Dr. Bateman's launching of OFFER. The organization's successes include:
OFFER's warm relationships with all CFS Associations, the Fatigue Consultation Clinic, and the University of Utah allow its members to have access to the latest information throughout the nation and the world, said Milne. The clinic, for example, will conduct FM drug studies for several pharmaceutical companies while continuing to be one of only three sites offering ampligen treatment for CFS patients. The University of Utah is also conducting groundbreaking research, and several OFFER board members have passed along information to these scientists through education meetings, e-newsletters, and conferences. Milne used a personal story to illustrate the effect of OFFER outreach. She was referred to Dr. Bateman by a physician whose daughter had FM. The physician admitted to Milne that he did not believe that CFS and FM were physical illnesses. He said that he tried to raise his daughter's spirits and encourage her to try harder, be grateful for what she has, and push on with her life. He encouraged Milne to do the same. That doctor attended OFFER's first conference in spring 2002. He left a changed father and doctor, said Milne, after hearing clinicians and researchers talk about the physical devastation that comes with CFS and FM. He asked for and received his daughter's forgiveness and shared his findings with her husband, who was also a "disbelieving MD." Milne handed a brochure for the 2007 OFFER conference to a neighbor, who began crying on the spot, admitting that despite her family doing the best it can, "mostly I suffer alone. I feel so isolated." The woman attended the conference and left "with a very big smile on her face…and lots of educational materials in her hands." Milne told the committee that OFFER's model is effective and its successes with advocacy, patient education, and research should be shared with the other regions in Utah and other states. She concluded that with adequate financial resources, OFFER's model could be duplicated, offering hope to patients, helping families understand the illness, and informing providers about diagnostic and treatment possibilities for CFS. Committee Members Q&A Dr. Oleske commended OFFER's work, then asked for the breakdown of the group's 2000-person database by age, noting that school systems are often unreceptive to a diagnosis of CFS in adolescents, and elderly patients are seldom discussed. Ms. Milne: There are no breakdowns available. At nearly 65, I am one of the oldest people in the database. We have a pediatric problem with CFS in Utah. One of Dr. Bateman's PAs and a psychologist in the Salt Lake area meet from time to time with teenagers and college students with CFS and FM. Just from eyeballing conference attendees, I conclude that I'm on the high end of the age scale, but there are many teenagers and college students who are burdened with this illness. When I look out into the audiences attending education meetings, I see a lot of people probably in their 40s and 50s. My personal concern about research moving forward for CFS is not so much for myself, but for the young people who I keep meeting who are desperately trying to get through high school and get their college education. I meet people who are beginning families who are suffering with CFS while raising young children. Dr. Jason: The National Institute on Aging (NIA) is sponsoring a conference on fatigue that will include Dr. Gudrun Lange. That might be a contact person at NIA who might have a lot of interest in CFS. Dr. Hanna: I will also be attending. Dr. Jason: I am intrigued and excited by your comment that the OFFER model could be replicated in other places. Have you made any efforts to secure the funding to do so? If not, what are the barriers? From what you're saying, if we had 20 sites like this around the country, it would make a big difference. Ms. Milne: I am hoping that that becomes the next focus of our board. I know that I share this view with at least some of the other board members. I got a feel for it when I was sending PSAs and press releases around the state. I talked to editors of small papers that represented communities that are not heavily populated and heard that there is interest and need. Through our efforts, I think that we really have encapsulated the most important activities in reaching our constituency. I do feel personally that it is packagable. We have not asked for money to do so; I don't know where we would ask, but I know we will find out. If any of you have ideas, I would like to take them back to my board. Dr. Klimas: I had the pleasure of attending several of the OFFER events, including the most recent one. The thing that I came away with was the intense interest of the providers. What they want to come away with is walking orders on how to treat this illness appropriately. This is an extraordinary conference and the providers were given exactly what they need to go back and start taking care of patients. Even if they've never taken care of patients before, I think that they could have walked away from that conference knowing how to approach the illness. That was a very packagable agenda. I think it absolutely has to be done. The CDC/CFIDS outreach is a wonderful program in a one-hour format during grand rounds, but it is like the "open door." A full day or a day and a half conference for providers that can be offered regionally, would be well attended. Ms. Milne: That is the importance of having a standard bearer like Cindy Bateman. OFFER would not be the kind of organization that it is without her point of view that when we talk to patients and providers, we must give them how's and what-furs. Providers must leave conferences with know-how. Dr. Papernik: Why are the providers in Utah more interested in going to these conferences as opposed to those in other states? Are they getting [Continuing Medical Education (CME) credits] for this? Dr. Bateman: They are. We make this a multi-disciplinary conference, and offer at least six kinds of continuing education for nurses, social workers, psychologists, physicians, and family practice doctors. We've done it through a different CME provider every year on purpose to involve more institutions in this effort. We've used a major health care company and we used the Utah Medical Association last year. This year we did it through the VA, which is involved with the university. Because of this, the university wants to host the conference the next time, which is a huge advance. It isn't easy to attract providers. The key factors for success are:
Dr. Papernik: It sounds like Dr. Bateman sees every CFS patient in the state of Utah. If most of these people in the group (OFFER) are her patients, then she probably has the database that Jim (Oleske) was looking for. Dr. Bateman: My patient database and the one for the conference are completely separate. I am able to use my mailing list to send things myself to my patients to advertise the conference, and so are the other professionals on our board, which is helpful. Dr. Snell: One other thing that an organization like OFFER can do for potential research is provide a database of patients. We can only do research if we can provide subjects, and sometimes that can be difficult. It can be helpful to educate providers to refer patients for research purposes and also for patients to volunteer. They get to understand how important the research can be and how important their cooperation is. We've even traveled to Utah to access Cindy's patient database because we sometimes struggle to find enough patients to populate a study. Dr. Bateman: At the conference we've had patients volunteer to be on a research list. When we hear about it, we'll list it, allow patients access to the information, and then they can pursue it on their own. It has become a great resource for the university, for example. Mr. Newfield: Given that the VA was involved in the OFFER conference, does that help in any way in packaging this regionally? It may make it reproducible if you're linking with another agency. Dr. Bateman: The VA has great resources because they could email everyone. The costs were entirely different. The VA provides the CME free to all CME employees. We were able as a nonprofit to do better financially on the conference. Sometimes commercial CME departments keep all of the money after doing a conference. We had a great partnership with the VA and they increased our resources tremendously, especially in the ability to attract people to the conference and their affiliation with the university. Ms. Healy: I was curious about what work OFFER might do with providers in training-physicians, PAs, advanced practice nurses, or others. Do you have relationships on the education side of things? It sounds like you have a wonderful foundation of a network of both patients and providers. Would OFFER members consider becoming patient instructors who would talk about CFS to students in training? We've heard at our meetings since I've joined that there is a lot of bias in the provider community. Perhaps getting trainees to have a one-on-one discussion with a patient may be a way to begin to break down these biases. Ms. Milne: That is one of our successful actions. After we print the provider brochure for the conference, for example, in addition to mailing them to doctors, we get them into the hands of patients so that they can take the brochure to their own primary care doctor and have the conversation that you are speaking about. Our education meetings are sometimes directed towards educating patients to better present their case to their doctor. Dr. Bateman: We do have one board member (a nurse midwife who works at the university and has a daughter with CFS) who has taken it upon herself to set up speaking engagements for me and for other speakers. She has set up eight or 10 such engagements for me last year with providers in training. Dr. Oleske: Let me take a second to introduce Dr. Hartz, who has now arrived and is the fifth new member of CFSAC. Dr. Hartz: How do you help patients and physicians in remote areas that are far from Salt Lake? Ms. Milne: That is part of our future focus. We have spent a lot of time in these last five years trying to build a relationship with the University of Utah in Salt Lake City. Since most of the people who receive our services are in Salt Lake County, that is where we have spent the most time. We do have an interest in penetrating the state and reaching those doctors. We know there are patients there because they come to our conferences. Dr. Oleske introduced Dr. Joseph John (see page 23) who has worked at the VA Medical Center in Charleston, SC, for five years and in New Jersey for 10 years before that. Dr. John: Linda's comments are reminiscent of what has gone on in New Jersey. The model that I can think of for what sounds like a great need to regionalize these activities-as has been done in Utah, New Jersey, and perhaps other states-is the Infectious Disease Society of America. The effort has been to create statewide societies. Those have been very successful and have resulted in annual statewide meetings. Without that kind of unifying, consistent regional representation that also serves as an outlet for provider education, it's very hard to get things moving in a state, find cohesion in how to educate patients, and establish continuity of care. Dr. Oleske introduced the next speaker, Patricia Fennell, from Albany Health Management Associates, Inc., noting that the organization is dedicated to improving the quality of life of patients with any chronic illness. He added that CFS causes tremendous negative impacts patients' quality of life, and one reason why physicians need to pay attention to treatment symptoms-"which we sometimes don't do"-is to improve quality of life. Patricia Fennell, Albany Health Management Associates, Inc. Ms. Fennell presented at the OFFER conference several years ago in the area of chronic disease, sexuality, and the impact that it has on couples and families. Her organization has been treating chronically ill patients since the late 1980s. It has conducted research and theory building, treated patients at the clinic, and handled comprehensive case management and policy work. She expressed hope that part of the message she's sending is that others might also be interested in the kind work done at the Albany clinic. The environment has change enormously in the 20 years of treating CFS and FM patients, particularly in the last five years, said Ms. Fennell. There has been a paradigm shift in medicine from an acute care system, which is still out there, to a chronic illness system. The health thrust has shifted from narrowly focusing on one disease at a time such as arthritis, diabetes, and congestive heart. This is the larger environment that CFS patients are now part of. It stresses the necessity of chronic care models, and there are only a few of them out there besides our four-phase model. The paradigm shift has had good and bad impacts on CFS patients. It is beneficial for chronic illness to be a focus, but she wants to make sure that CFS patients aren't left behind. Considerations when comparing chronic vs. acute illness:
It can be argued that medicine is having trouble adapting to the chronic model of care. Chronic patients are having trouble coping in an acute, episodic care delivery environment. How can we improve the tight coordination of care over multiple disciplines? Cindy [Bateman] mentioned that part of the success of her conference is that they do a multi-disciplinary approach. When you talk about chronic illness, said Ms. Fennell, you really are talking about not only the physical aspects, but the psychological and social aspects and how they affect an entire family:
Why the paradigm shift to chronic illness? The increased prevalence of chronic illnesses in our culture. In 1995, JAMA (Journal of the American Medical Association) reported that half of the U.S. population had a chronic disease, not counting mental illnesses. CFS patients are part of this growing population. We have an aging population. In Albany, NY, the average life span in 1922 was 53 years; now you will live to be in your late 70s/early 80s due to public health, antibiotics, and technological advances. Four groups of chronically ill:
CFS patients are going to be embedded in these larger groups with everybody competing for dollars for treatment. Historically there has not been a lot of coordination across multiple settings, providers, and treatment in managed care. It's like the Wild West out there. There are all kinds of services being considered, but there is not a lot of coordination between them. The Fennell Four Phase Treatment (FFPT) Approach Research is being done on this model in a variety of places in the United States, including Cornell Medical Center, as well as in Belgium. Several things must be stressed about the philosophy of the Phase Approach: We assume integration versus cure. We can't cure folks of a chronic illness. So how do we help them build a whole life? How do we work with their new norms so that they aren't a person attached to an illness, but a person who has an illness within the context of larger life? We assume that the disease experience is traumatic in and of itself. Ms. Milne said that she has been asked over the years if CFS patients are abuse survivors who are now presenting with illness. She answers, simply no. The numbers of CFS people who have been treated in Albany over the years who also have histories of trauma are similar to cancer or AIDS patients. The types of trauma experienced by CFS patients are:
All of these things act concurrently on the patient's experience. Part of Albany's research is looking at particular social/cultural factors that impact the CFS patients' experience. Two of these are the cultural intolerance of suffering and the cultural intolerance of ambiguity. CFS involves many unknowns. People are going through cycles over and over and everyone around them-provider, family-gets to go on the ride with them. The Four Phases of Chronic Change The phases of change in a chronic disease are: crisis, stabilization, resolution, integration. Each phase has three domains-the physical/behavioral, the psychological, and the social interactive. When most patients come in for treatment, they are in the crisis or stabilization phase. Most patients loop between crisis and stabilization because they are always being encouraged to and want to return to the pre-crisis life. They must be assisted with moving on to resolution, otherwise they set up an ongoing cycle of relapse by doing too much and trying to use the same norms that would apply before they became ill. Phase I - Trauma/Crisis Physical/Behavioral - could have a rapid or slow onset, but in either case, patient ("Betty") begins to notice changes in the activities that she can perform physically (climbing stairs) and cognitively (cannot operate common machinery such as a television or telephone). She tries to cope until she is at the acute/emergency stage of this phase and can no longer escape the symptoms. She seeks care. Psychological - Patients typically have a loss of psychological control-an ego loss. Everyone has a private and a public self. When people begin to experience the onset of an illness that is this significant, those two arenas begin to blend. Depending on the severity of the onset, it can be a devastating experience triggering intrusive shame, self hatred, despair, shock, disorientation, and disassociation. It's typical for a patient to have a fear of others. Social/Interactive - Those around the patient can experience shock, disbelief, or even revulsion, depending on the severity of the symptoms. They can be vicariously traumatized. How difficult this crisis phase can be depends on the family's maturation. Physicians in settings that limit the amount of time that can be spent talking to patients ask how they can treat CFS patients within such limits. The severity of this phase also depends on how much support or suspicion the patient and family receive from their peers, workplace, and clinicians. Belgian researchers report a crisis phase that is shorter by several months than that in the United States. Belgian patients did not have to negotiate the disability, work, and financial issues to the degree that U.S. patients must. Phase II - Stabilization/Normalization Failure Physical/Behavioral - The patient is not better, but is beginning to carve order out of chaos and understand what her symptoms are. She is beginning to understand how her disease is functioning (i.e., how often she can climb the stairs). Psychological - Patients exhibit increased caution and secondary wounding. They begin to withdraw and search for others of like kind. As people stabilize, they begin to look for others who can give them information and understanding about their experience. There is some boundary confusion (person with a disease or disease with a person?) and service confusion, where patients are trying to work with their local clinician, but can't find appropriate services. Social/Interactive - There is either increased cooperation or conflict. It is not unusual for a spouse to declare, "I did not sign up for this." Ms. Fennell explained that we are not trained as a culture to think that we are going to get chronically ill. She has yet to see a patient go through this process and not lose someone who is significant to her. The kind of divisiveness that this creates in families is huge and expensive (lost wages, divorce, etc.). As a result, patients try very hard to be who they used to be, often resulting in normalization failure. Phase III - Resolution Physical/Behavioral - There is an understanding that relapse is part of how chronic disease functions. Psychological - There is imposed change that people do not want to make. To recognize that they can't have their pre-crisis life takes a huge psychological jump. It is in this phase that a true grief reaction sets in. People in the crisis phase are frightened, depressed, or angry. In the resolution phase, they begin to grieve for their pre-crisis self. This almost always has to be done with assistance. This is where people are most at risk to commit suicide and abuse substances to cope. To recognize the level of change that is required is huge. If people are to shift, they have to develop meaning about their suffering. It is important both medically and emotionally to match interventions with the phase and stage in which they will be most effective. At Phase III, when people are dealing with grief issues at a much higher level, they need different types of techniques. What a patient looks like in year one and what she looks like in year eight is not the same. The people around her do not look the same. Social/ Interactive - We see patients engage in a whole variety of things, such as becoming invested in doing different kinds of advocacy work. That is one choice for people. They may engage in different types of role experimentation, including retooling for a different job. This is where there occurs a reintegration or permanent loss of supporters. Some of the people who patients reached out to in Phase II become integrated into their lives. Phase IV - Integration Physical/Behavioral - Patients have an expectation of relapse and remission. Psychological - Patients have developed a new role and identity. Social/Interactive - There is new integration of supporters. People do not go through the phases in this model once. It functions like a cognitive map. There is not a lot in the media about chronic illness and what people can expect over time. Part of what we teach is that if you go through the phases once and you get assistance and you do it successfully, you're better prepared for what comes next, whether it's a relapse, a different disease experience, or a normal developmental stage of life. Traumagenic Effects Intolerance of chronic vs. acute syndromes: The dynamics of intolerance include pressure for a "cure"/normalization, lack of treatment models, frustration conveyed by those trying to provide treatment, punishment for healthy self care and rewards for unhealthy self care. The effects of intolerance include normalization failure, increased salience of abuse issues, avoidance of intimacy, and social withdrawal. Ms. Fennell said she would like to see the U.S. reach the point where CFS patients don't have to pretend they don't have CFS in public or lie about having CFS so that they don't experience stigmatization. Treatment The Albany clinic works hard to match intervention to phase, and sets treatment goals at each phase. Case management is very specific. Evaluation includes medical protocols, coordination with clinicians, psychological support and intervention, self management, and disability issues. Albany also trains medical professionals of all types and would like to train more. Each phase has a clinical goal and a case management goal: Phase I Clinical goal - Trauma and crisis management-get the patient contained through BATOS so that the disease process doesn't get any worse: Bond - The type of bonding required from a psychological perspective is difficult when the patient is covered by health insurance that requires that this occurs in nine visits or less. Case management goal - Establish a case management focus. Restructure daily activities, conduct family case and health care system management, and develop training and interventions for the workplace. Phase II Clinical goal - These patients have to learn how to be different people and that's a big job. The goal is stabilization by teaching patients CDIN: Collect data. Case management goal: Data collection and activity restructuring. Also included are helping patients develop new norms, case management of family and health care, and clinician advocacy. Phase III Clinical goals - Help patients develop meaning about this experience and construct a new self through GMR: Grieve - Human beings need a story to help explain why they've gone through this trauma and why they should bother to continue to so, or people just don't want to do it. This is part of the necessity of grieving and differentiating this from the clinical issues of depression. Case management goal - Self management skill development is key. Patients need to learn how to monitor their own activities-how they walk, how are they eating, what their symptoms are. Patients also get help with medical coordination and learning how to be their own advocates. Phase IV Clinical goal - Integration. "It is what it is." Case management goal - Facilitate patients learning how to do their own self management. Committee Members Q&A Dr. Oleske: What you have presented is a comprehensive way of managing someone through a chronic illness. How is that paid for? How do people access that? Ms. Fennell: Some of the services are paid for through insurance as a psychological service. We've have varying success getting payment for case management. The case management that patients could have done in conjunction with their primary care physician years ago just isn't available anymore. These cases absolutely need to be case managed, and that's not paid for, so that is something that we would like to see changed. Dr. Jason: Patients frequently mention that they have a very short time when they see their medical practitioner. Often medical practitioners talk about getting punished for spending more time with patients who have complex issues. How does one deal with those system issues that now affect patients with ME/CFS that allow them to have the time to go through the type of treatment and management that you're talking about? For cancer and MS and some other illnesses, you do have centers that you can go to get that kind of comprehensive treatment. Is that something that you think might be needed in this field? Ms Fennell: The truth is that almost all of the chronic diseases are having the same struggle, and part of my concern is that CFS doesn't get lost in that morass. I think we're looking at a time where the whole healthcare system is struggling with being retooled, moving from an acute care system to a chronic care system. Currently, it's organizations like mine that are trying to provide a stop-gap measure in case management to work with the physicians and clinicians, because the system does not exist. Part of what we're trying to do is create a discipline that works along side of the primary care providers in clinical case management. Mr. Newfield: At the OFFER conference, we heard a doctor from Sweden talking about being able to go out on disability ("burn out"), and how in the United States, they do not permit going out for disability from burnout. They would take the position that while you can't do that job in that particular place, you can do some job, and therefore wouldn't qualify. Is there any data from Belgium that we can look at and use to help advocate? Perhaps they can make a presentation to us. Ms. Fennell: That would be a good question to pose to those colleagues, and I can share that with you after the fact. Dr. Papernik: When the patient is being seen for the first time clinically, he is looking for a diagnosis. It is not going to be well received if I say, "I think you have a chronic disease. I want you to see a psychologist or psychiatrist to go through these steps to learn how to deal with your illness." Ms. Fennell: You make a very interesting point, that when someone first comes to you and they may in fact have a chronic illness, but you have no idea yet, that would not be the time to introduce them to this model. Dr. Papernik: That's my point, that this is a model that needs to be used once a diagnosis has been made, knowing that what lies ahead is these stages. Ms. Fennell: It could be a lengthy process of diagnosis. You may have to put them through months of testing. You might have a diagnosis that you start with; you may need to reframe it as time goes by. I would advise folks to consider starting this process if you're several months in. If someone has been flailing around with their symptoms for five or six months, they need to begin to have some intervention on this level. Dr. Oleske: Thank you for a wonderful presentation…I have asked Dr. Joseph John to come as my guest. He is an outstanding clinician. He and I wrote the New Jersey Management of Chronic Fatigue Syndrome Manual that has been adopted in Vermont and some other states. My concern, and one of the things that I hope we accomplish as a panel, is to change the paradigm so that patients with CFS receive treatment for their symptoms. What I find, unfortunately, is that a CFS patient can have all of the symptoms of a seasonal allergy, but they are being ignored because they have a chronic diagnosis. Update on CFS TreatmentDr. Joseph John, Jr., Veterans Administration Medical Center, Charleston, SC Dr. John provided a review of where the field has been over the last several years rather than just a focus on treatment. He commended Pat Fennell for presenting a truly holistic framework in which to start thinking about teamwork in treating CFS. He thanked CFSAC members for the data that they have provided and produced over the years in their studies. The term "fatigue" has some interesting historical frameworks, he continued. It probably had its origins in the industrial revolution, since it was not a legacy of human behavior coming up through that time. The term did not start to pervade the literature until the 19th century. In Japan the condition is called a cytokine syndrome, because it suggests a mechanistic basis. Diagnosis Dr. John said that he guides patients through a thorough self-inventory before deciding on their treatment. He may ask a patient to construct a graph where 10 is good and zero is bad. There are other rating systems, including a quantitative one that Nancy Klimas and some of her colleagues have been working with internationally. Some of the multi-dimensional fatigue inventories could also work well, he said. The SF-36 Form is something that could be used more commonly than is the case, but it is very hard to do in a 15-minute visit with a busy primary care practitioner. Dr. John consults a flow chart in his office that depicts the steps toward diagnosis and checks them off as he goes. He added that it is valuable to have individual appointments focusing on different aspects of diagnosis. Dr. John echoed Dr. Papernik's point that a lot of differential diagnoses have to be ruled out, and this takes time. Dr. John said that for the last decade he has been attracted to the idea that there are some specific anti-viral mechanisms available to cells that have to be overcome in viral illnesses that use host machinery as a basis of their pathogenicity. This idea of a channelopathy gives a totality of diagnoses to explain the expansive symptomatology that CFS patients have, he said. A patient could have defective anti-viral machinery that could relate to membrane destability. These ideas assist in understanding the dysfunction of amino acid building blocks and the type of pain symptoms that they might relate to. When faced with colleagues who say, "This is not a disease," Dr. John's response is, "Do you believe in congestive heart failure?" which is simply a gross syndrome of cardiac dysfunction. CFS is a set of criteria that fit a large number of patients' illness and Dr. John said that he carefully categorizes them not only for therapy reasons, but for disability and psychological rehabilitation. There is fascinating epidemiology for this disease, he continued. Data from a Dutch study of French and Belgian soldiers returning from Cambodia with CFS-type symptoms show 19% recovery, 20% improvement, and 57% with delayed and continuing complaints. There are other data generated by the Persian Gulf War, said Dr. John, but there has not been a good follow up on the clinical symptomatology. When a patient says that "It all started when that horrible hornet bit me back in '95 and I never got better," how does one put that into a whole framework? But it must be done. There are other more serious, provable surrogates of initiating disease like toxoplasmosis or HHV6. Dr. John said that he likes the idea that predisposing factors imply some genetic basis-that there are initial environmental factors that patients come into contact with and respond differently to in terms of complaints. So there are predisposing factors, initiating factors that feed into patient complaints, then perpetuating factors. One question is, how much lab work must be done for a CFS diagnosis? In this age of HIV and retroviral illness, we can start to talk about cellular dysfunction. One constant construct in this disease has been NK cell decrement in number and function. That has been a valuable place to go if patient's insurance will pay for it and a physician can get a lab to do it. There are several HHV6 labs that have shown a large overlap for this illness. Dr. John suggested that as more is learned about HHV8 in interaction with HIV, it will open some new doors for more study of HHV6. He added that researchers are also advancing towards more understanding of the pathophysiology through imaging. Japanese colleagues presented broad-based brain imaging findings at the 2005 CFS conference that reflected back to earlier studies suggesting deep changes in white matter. There has been a legacy of dysfunctional anti-viral machinery. Dr. John reiterated that there may be some kind of final common pathway for channel dysfunction, which is at the basis of many illnesses today. The bottom line: There are probably multiple viruses involved in this disease, there is certainly a genetic predisposition, and there's a broad-based cellular response to whatever physical or microbiological trauma has evidenced. Work coming out of CDC on gene expression suggests abnormalities in down regulation of sets of genes in transcription cell cycle and less up regulation in areas of other metabolic functions. Dr. John offered other thoughts on diagnosis including:
Treatment Dr. John addressed the role in disease management of less well proven treatments like acupuncture and psychotherapy, noting that he liked how the Observer article handled herbal and over-the-counter therapies by saying that they do work for some patients. He said that there is hardly an acknowledgement of that in the literature. Dr. John noted, however, that patients do not always have access to recommended treatments like psychotherapy. There are only three psychotherapists in Charleston, for example, and it's a pretty big town. Patients may wait months to line up their treatments, referring to Ms. Fennell's presentation as illustrating the necessary level of sophistication and organization for doing so. As far as pharmacological therapy, Dr. John said that many options are at a physician's disposal. There is ampligen therapy going on, and while researchers may not have totally discarded the micro plasma hypothesis, there are many groups of drug classes available and newer agents coming onboard. One generating excitement is cyclovere, particularly as it would be a herpes virus group stabilizer. Also being studied are anti-dementia drugs and those used for bipolar and other chronic brain diseases. There also may be a role for magnetic therapy, including a way to titrate a diagnosis with magnets. Dr John cautioned, however, that working with some of the newer stimulants coming on the market may be problematic because the long-term affects are unknown. He also noted that bipolar disease is becoming much more prominent in the consciousness of clinicians who treat CFS patients, particularly as it affects their psychological adjustment. A CFS patient without bipolar disease can come to a new self-realization in a way that bipolar patients are blocked from. Dr. John noted other aspects of treating CFS including:
Dr. John concluded with his hopes for the future:
One of the challenges of CFSAC and a basis for comprehensive and multi-center studies is invoking the practicing community into taking care of CFS and studying that is best done. The medical investigative challenge remains. Committee Members Q&A Dr. Oleske: You, Ms. Fennell and others are advocating a comprehensive approach using different disciplines and good rehabilitation including medication. The thing that troubles me is that one of your clinics was closed for financial reasons. Can you talk about what happened what it implies for other facilities and a new generation of medical people? Are they going to be attracted to a field that has such economic consequences? Dr. John: It's very tough. In a nutshell, there's got to be departmental support from the top. If you try to initiate these kinds of efforts from the bottom, you're crawling uphill. We all know what the chairmen of these academic departments are like today. They need to be handed a workable business plan that is viable. How few of our junior colleagues can do that? They're not raised as business people, but they need to collaborate more with the business people. Another way to garner support is to avoid being seen as working in your own enclave, because that makes you vulnerable. The CFS activity in my facility was vulnerable to closing because it wasn't intertwined with endocrine, pediatrics, or even infectious diseases. Dr. Klimas: I had similar financial issues with my own department. When I presented it to my chairman as a community service for an unmet need of the community, I hit a different tack. A medical school is one place to set up these center models, and part of medical school funding is often meeting the needs of the community. Dr. Oleske: One of the recommendations that CFSAC has made already is the concept of clinical centers of excellence and clinical trials located regionally. [Dr. Oleske called a five-minute break.] Dr. Oleske: As a pediatric immunologist, I only have the greatest admiration for Dr. Krensky's achievements in transplant immunology and taking care of children. He's going to be talking about the Roadmap Initiative. I hope we realize what a wonderful, generous opportunity this is from Dr. Krensky to find out how we could have CFS placed on that Roadmap. Update from NIH - Roadmap InitiativeDr. Alan Krensky, Director Designee, Office of Portfolio Analysis and Strategic
Initiatives (OPASI), National Institutes of Health Shelagh Galligan Professor, Stanford University Dr. Krensky noted that he will formally start in his job as the new Deputy Director of NIH and Director of OPASI on July 8. He explained that the NIH Roadmap Initiative will reside in the brand new office called OPASI, and that there is both good news and bad news for CFSAC under the OPASI approach. The first omnibus reauthorization of the NIH in 14 years just occurred. Congress passed it in December 2006 and President Bush signed it into law in January 2007. The NIH Reform Act of 2006:
OPASI's Mission
Structure of OPASI
There are three divisions within OPASI: Division of Resource Development and Analysis includes portfolio analysis, which has two major pieces-
Division of Strategic Coordination, which includes the NIH Roadmap, will also deal more broadly with strategic coordination of the 27 ICs. Division of Evaluation and Systemic Assessments will conduct governmentally required evaluation procedures assigned as part of NIH's responsibility. In addition, the division will launch trans-NIH initiatives that use state-of-the-art techniques to conduct effective evaluations of all NIH programs. OPASI was created so that portfolio analyses, strategic initiatives, and evaluation all interact and inform each other. At the same time, OPASI is a service organization dealing with the 27 ICs and how they should interact in cross-cutting, coordinated ways. It is not going to be a place with line items for particular disease like you would find in a Center. Many advocates believe that their illness is not represented at NIH and are hoping that OPASI is a place for such representation. This is not the way that the process works. The OPASI Common Fund will be contributed to by the various ICs, but for the first year, Congress provided $480 million as a line item in the NIH budget. The Common Fund will be used specifically to fund Roadmap Initiatives. A Roadmap Initiative must demonstrate:
NIH goes through the process of choosing initiatives every two to three years. Under the current timeline:
Of the $480 million, there is only $30 million available for new projects. Areas have been selected for discussion. They are not yet RFAs (requests for applications). On Friday, May 18, the IC Directors will vote on areas that warrant further evaluation before RFAs are developed in the fall. Although nothing in the Roadmap is disease-specific, all areas have implications relevant to CFSAC and the committee should be excited at the tremendous potential. CFS is one of the diseases for which the Roadmap topics could have huge implications. These topics have not been finally selected and they may not all make it into the Roadmap this year- Potential Roadmap topics under discussion: The microbiome is an exciting concept that has come up over the last couple of years. Probably the most provocative piece of data is that researchers can take the microbes from the gut of one animal, put them in another animal, and have that second creature go from being fat to thin. The human body has more microbial cells than human cells. NIH proposes to start sequencing these microbes, defining the panoply of microbes that inhabit the human body. A lot of work has been done in the gut, but every orifice of the body has a group of microbes. These are highly likely to tell us about a number of diseases, including CFS. Inflammation as a common mechanism of disease. The immune system underlies the majority of human diseases in one way or another. Protein capture agents and proteomics. The genome project revealed a lot about genes, but researchers are just beginning to learn about proteins. One gene can give rise to many proteins. Because proteins are much more diverse than the genes, proteomics is an area of great importance. Standardization of human disease phenotypes. Not everyone does a blood pressure test the same way, meaning that when these blood pressures are reported in studies, the results are not standard. This is mundane but important if researchers are talking to each other about data. At the other extreme of these phenotypes-and I'll use the immune system as an example-no one has discovered a biomarker for CFS. We really don't even have biomarkers to measure how well the immune system is working. Epigenetics. The genes exist and they code for proteins, but epigenetics-other enzymatic effects-affect the genome in which genes are turned on and turned off. A lot of work has been done in this area, but researchers have come up against many roadblocks. New technologies are needed to understand how genes are turned on or turn off. OPASI is not just about the Roadmap, but other trans-NIH cross-cutting areas. The most important areas at this point include: Obesity, which is the biggest public health problem in this country. Remarkably little is understood about it, but it is an important behavioral target. It's an area to which NIH has paid relatively little attention. There is a fledgling obesity initiative, but it is underpowered for what it has to do for the American people, said Dr. Krensky. Neuroscience Blueprint runs a close second to obesity in priority. NIH has seven core neuroscience Institutes and 17 involved in what is called the Neuroscience Blueprint. The potential for big, bold, new views of how to deal with things like pain or chronic fatigue really lies in this constellation of interaction dealing with a variety of disorders, said Dr. Krensky. Regenerative medicine has become a catch word for everything from battlefield wounds in Iraq to the idea of taking fat cells from your body and making new brain, kidney, or liver cells out of it. Regenerative medicine is a broad area and a real opportunity for all the agencies within the department to work together. Informatics (information systems) underlies everything. This goes from bioinformatics, which support things like microarrays, to medical informatics and how records are moved from paper to new interconnected information systems that help provide up-to-the-minute bedside care up-to-the-minute. Pharmacogenomics is an area that almost every Institute within the NIH is working on. There is a lot of potential for collaboration when looking at how drugs relate to the genes of each individual. Health disparities include those associated with race, sex, and socioeconomic status, the last of which is one of the biggest health issues in this country at this time. A children's health initiative(?) This is a less developed concept than the others. Congress has funded a National Children's Study that has just started and is looking a genetics and environment and looking in a prospective way. There are several institutes within NIH that address children, but they don't really work together as a cohesive whole. How will OPASI likely affect trans-disciplinary research?
Factors for success
Committee Member Q&A Dr. Glaser: You can put as much money as you want into programs doing multi-disciplinary research, but if you don't have people on study sections who understand that, you're going to have a problem. That's what came out of a meeting that took place a few weeks ago at NIH that examined the study section program. There was consensus that the general structure of study sections is fine. The problem is that the membership of those committees wasn't able to do multi-disciplinary reviews, which results in good ideas not being funded, including those related to CFS. What is your comment about that? Dr. Krensky: You're right on in all of this. It is essential to the NIH structure that peer review and program decisions are kept separate. There's a firewall there and that will be maintained. That being said, peer review is on hard times for several reasons. Everyone agrees that peer review is the best thing that we can do. But with the doubling of the NIH budget, there was a doubling of the number of grant applications. Study sections that had 20 people now have 50. Study sections that had the same senior people consistently conducting reviews now have ad hoc members. There is a blue ribbon committee as well as an internal committee generating ideas to solve the problem. One idea is to review proposals based on the peer review journal model where a large group of people do the initial reviewing, then feed into a smaller group of senior experts. NIH will conduct pilots before changing its study section system. We realize that our current system encourages reviewers to make "safe" choices. Dr. Jason: When you have 15 or 20 people on a review panel, there's no way that they're going to have the expertise for 100 areas, and I think that's the basic problem. The review journal approach is a brilliant idea. I had a question on the $30 million and what percentiles are going to be available for the number of proposals coming in. There is also a larger issue: CFSAC is a good fit with what you're talking about. We are multi-disciplinary. The things we're interested in are broad and affect multiple diseases that we have expertise in. One of the problems is generating enough study subjects to look at the subtypes and small phenomena that we're interested in. Is it possible with some of these Roadmap Initiatives for collaboration across sites in different locations in the country to get what we need for our research? Dr. Krensky: There will ultimately be 60 translational science groups across the country based on a clinical trial infrastructure. They will interact with each other and they will not be disease specific. When they set up genomic genetics, pharmacogenomics, proteomics, etc., those will be available as an infrastructure to every disease group. OPASI and DPCPSI are going to try to build things that everyone can use. My take-home message is that OPASI, DPCPSI, and the Roadmap will have great implications for CFS. The goal is to try to get the neuroscience blueprint to work together. Neuro, immuno, endocrine…we call these different systems and they're really not. The human body works as an integral whole, and I think CFS fits into that. CFS is a syndrome just as most of the diseases we deal with are syndromes. Heart, diabetes, and cancer are not one disease. What we're learning in the genomic era is how to subdivide these diseases. That's what's going to happen with CFS as well. The real answer to finding therapies and the biomarkers to diagnose the disease is to start subdividing it. OPASI is fostering a new kind of research different from the hypothesis-driven research that NIH was built upon. The diabetologists might find the cure for cancer, and the cancer doctors may find the cure for CFS. These are all overlapping. That's the reality of the biology. It's a change for NIH. I'm not saying do away with disease specificity, but we have to work together because there is a lot more that we can get with these cross-cutting ways. Dr. Klimas: The Office of Women's Health put out an RFA on CFS and got four or five times the proposals expected in an area desperate for new people. How is OPASI going to affect the Office of Women's Health. Are they going to be able to get money through that mechanism? Dr. Krensky: Within DPCPSI, all of the offices of the director are put together. There are no announcements yet about what it's going to look like, but included in those are OPASI and the other programmatic offices like Behavior, Women's Health, AIDS, and the Office of Disease Prevention, which includes rare diseases and dietary supplements. These are areas that didn't fit into any other group and went into the Office of the Director. But they're all inherently trans-NIH and cross-cutting. Congress does not want any more programmatic offices just like it doesn't want any more Institutes and Centers. Any new areas to be studied will be through functional integration, not structural. I think that the mechanism that was used by Women's Health to specifically fund CFS is an example of the system working really well. The biggest issue for Women's Health and all of NIH right now is that we've had a shrinking budget in real terms. It is difficult to develop new programs or add new programs when your budget is shrinking. There are lots of really good new ideas-more than ever out there-but we need the money to implement them. I think that Women's Health, if asked, would tell you that they're happy with how the RFA but their reality is that they have less money than they had last year. I think that in a shrinking budget, all fields are at relative risk. Some already have a lot of money and others don't. The NIH is ready to have a huge impact on public health. This new office is designed for that. This is a new way to approach things, and with new moneys going forward, I think there will be a huge impact, but the NIH budget, since the doubling, has gone down in a dramatic way. I think we've never had an opportunity to do more for CFS, but money is the oil that makes the machine run. Dr. Oleske: In this trans-NIH program, how is the individual investigator-driven proposal going to be treated? It's hard for an individual investigator to write a proposal that encompasses this trans-NIH potential. Dr. Krensky: Investigator-initiated awards are the gold standard of the NIH. Everyone thinks that's our priority. Within the Roadmap in particular, we may build the infrastructure, but it will be the individual investigator who proposes to study CFS and the proteomics core. The Roadmap has its special review groups and they are all told that we're looking for something outside the box and trans-NIH. Under our current system, people tend to avoid pushing the envelope. Peer review often goes for the common denominator. One of the first things that OPASI is going to do is have a session about innovation. Dr. Snell: What I'm hearing is that if we want to tap into this fund, we need to rethink CFS and look at it somewhat differently. For example, we do a lot of research with exercise. Typically people with CFS don't exercise. So if we approach it from the perspective of obesity, use CFS as an example of inactivity, and look at why people may or may not become obese in association with CFS, that would be looked upon more favorably than a pure CFS approach? Dr. Krensky: That's my message. I think that's a good way to go, but I'm saying that it's not mutually exclusive. Someone can still submit proposals to disease-specific areas. But my own personal bias and what I think OPASI is about is this bigger way of looking at things. There almost isn't a disease that can't be covered in the Roadmap. It really is a very powerful way to jumpstart science, this collaboration. [Dr. Oleske called a break for lunch.] Update from CDC - CFS & CDC Organizational StructureDr. Joanne Cono (via remote telephone hookup) Dr. Reeves I am reviewing the CDC CFS program in general to set the stage for my colleagues. Dr. Cono will then speak on the organizational status of the CFS program at CDC and Dr. Fridinger will talk about the public awareness campaign. We look upon CFS as a complex illness, not as a disease. Diabetes is a disease with metabolic pathways involved. CFS is an illness from which various diseases spring. Ms. Fennell talked about 21st century chronic illness. We're looking upon CFS as a model of 21st century illness in terms of treatment and pathophysiology:
What is the objective of CDC's CFS research program? To devise control and prevention strategies for CFS. Prevention right now is out of the question because we don't know the cause and metabolic pathways. Control, on a public health basis, would be decreasing the morbidity imposed by CFS on the population. This could be measured by:
How do we do implement the CFS control strategy? What does control consist of? Using a simple logic model, you have sick people within the population, some of whom have CFS. You get CFS patients into some sort of intervention or treatment, and that intervention or treatment has measurable outcomes on a population basis and on an individual basis. Obviously the intervention must be based on a lot of knowledge. People need to be able to evaluate and diagnose CFS [right now there are no diagnostic markers] and they need appropriate management strategies. The CDC research program tries to work at diagnosis and management through:
Population-based studies are important because clinical studies only look at those people who visit the facility. Studying volunteers presents similar limitations. Volunteers "are generally those who run to the front" and are not like everybody else. If you want to know about an illness like CFS, you need to look at the population with a study in which everybody in the population has a known chance of being sampled. How might we study CFS so that we can generalize it to the United States? Dr. Jason's group studied CFS in Chicago and the CDC studied it in Wichita. We had some differences in what we saw and we couldn't be certain why those occurred. The CDC is currently conducting a study in Georgia that includes the Atlanta/Macon metro area and the surrounding 12 rural counties. We have done a random survey of people in those areas through phoning 10,000 households:
Population Surveillance Results:
We have finished the baseline. As soon as the Office of Management and Budget (OMB) approves it-hopefully in August or September-we will do the first follow-up of this to look for incidence cases, look at the clinical course, and do a CFS patient registry. We are in the middle of the population survey, we know the occurrence of CFS in the population, we have gotten most providers (physicians, nurse practitioners, PAs, chiropractors, massage therapists, school nurses) to refer us all of their patients so that we can look at those people getting healthcare compared to the population. Emory University is interested in treatment trials and setting up a CFS center of excellence. We have looked at a fair number of providers for their knowledge, attitudes and beliefs (KAB) concerning CFS as well as the KAB of the general public and patients. Surveillance studies provide a lot of information, but the data they provide are limited to how much time you can spend with a large number of patients. Among the data gathered is that 48 percent of people going through the clinics who would meet the criteria for CFS had a readily diagnosable and treatable medical or psychiatric condition such as thyroid disease, diabetes, substance abuse, etc. In-Hospital Clinical Study of CFS Our in-hospital case control study will bring in 60 patients with CFS for three days to Emory Hospital. On the first day, we will conduct functional magnetic resonance imaging during a cognitive task. The second day, we will conduct functional magnetic resonance imaging looking for pathways involved during a cognitive stressor while drawing blood every 15 minutes. The third day, we will shut down the HPA axis with dexamethasone and give patients a challenge with corticotropic releasing hormone to see their various stress responses. This will also be monitored with 15-minute blood samples. What we can measure in the laboratory is the genetics. We know the genetics of the population in Georgia that we've surveyed. We can consider epigenetics (modifications in genomes due to life experiences) by looking at messenger RNA and we can look at the various proteins. Laboratory Study of CFS Everything we do involves lab studies. Blood is being studied from both patients who come into our clinic and those from the in-hospital study. We can look for risk factors, biomarkers, and pathophysiology: Plasma, serum, and PBMCs (peripheral blood mononuclear cell) allow measurement of exposure to infectious agents, proteins, cytokine responses, and immune function. Saliva lets you measure the cortisol (physiological stress) response. Researchers then have to put it all together. We know very clearly now that CFS is a mind/body type illness and involves the hypothalamic/pituitary/adrenal axis-we have a million data points on every patient. This comes back to the Roadmap Initiative. You have to put this together in a clinical context and you have to have the computational means to do that. It is very clear that CFS is not a single thing. It can include in varying degrees sympathetic nervous system involvement, change in the HPA axis, a metabolic component, etc. Returning to the control strategy: we have an idea of the burden and the morbidity, we know who is involved, we still don't have a clinical marker, but we have things that can be used pharmacologically for getting into the path of physiology. What of course is left out of that is the fact that only half of people with CFS have even seen a doctor and 16-20 percent have been diagnosed and treated. You've got to get those people into the healthcare system. This is where public awareness comes in. Once they're in, they must have doctors who can treat them and they must be eligible for treatment under their insurance policy. That is where provider education comes in. The information from the research goes to the provider education and public awareness efforts. Committee Members Q&A Dr. Jason: We've have heard that the CDC is having funding cutbacks. How will these affect your program? Has there been good epidemiology work on kids with CFS? There's been some controversy with the Wichita study using an empiric case definition vs. a usual way of doing that evaluation. Dr. Reeves On kids: CFS is primarily an illness of adults. It peaks in the 30-50 year-old group. It does occur in kids. It is perhaps more devastating at that time in one's life than it is for adults. Most of our research has centered on adults - that's where cases are and it's harder to deal with kids. Probably the most important group of kids is the teenagers. There's a real problem in dealing with people much younger than teenagers because they aren't acculturated yet and it's harder for them to express certain things. The provider registry is going to include all of the schools, all of the pediatricians, and the school nurses, so we are making an aggressive outreach to the adolescent population. On case definition: It is a sticky issue. CFS is fatigue not relieved by rest that causes a substantial impairment in occupational, educational, recreational, or social activities. It is accompanied by four of eight symptoms. The problem is-and it's been a problem in all of the studies-I really don't know how you defined CFS in Chicago compared to how we defined CFS in Wichita. We defined it the same way, but there is no standardized way to ask the questions about symptoms. What we have done more recently in our Wichita clinical study and in our Georgia studies was implement the recommendations of the International CFS Collaborative Group and use the SF-36 as a standardized instrument for measuring impairments. We used four of the eight scales. There is also the multi-dimensional fatigue inventory for measuring the dimensions of fatigue. We took two of the five scales. And then we devised our own instrument, which we published in Psychometric Properties, to measure the occurrence, frequency, and severity of the eight case-defining symptoms. Now our definition of CFS is that you meet at least one of the 36 SF criteria and at least one of the MFI criteria, that you have at least four symptoms, and that you meet a cutoff determined from the population. Now, what we call CFS is based on highly standardized instruments. On funding: Our current budget is $4.3 million for FY 2007, which is at about the 1992 level. We're doing what we're doing now because of money we had under the payback. We cannot sustain the program at a pre-1992 level. Dr. Klimas: If 85 percent of the patients are not diagnosed and half of them have not seen a doctor for their fatiguing illness, my question is about the other half. In my experience, medical care dollars spent prior to getting a diagnosis can be extremely high. I'm curious about what the healthcare cost is in the undiagnosed group. Dr. Reeves: When we did the study that we've published, we were able to calculate the direct costs. We're just beginning analysis in the Georgia study and measuring much more accurately the direct and indirect costs, and we will certainly relate that to those who are seeing physicians and those who are not. It will probably take about half a year to work that up, but it will be specific, including metropolitan, urban, and rural economic impact. Our calculation was that it costs the United States $9 billion a year in lost earnings. What's important to me is the $20,000 lost to a patient's family. Diagnosed or not, the people in Wichita were out of work and on disability. Mr. Newfield: With regard to the Georgia study, I hope quality of life issues will be looked at. Dr. Reeves: Quality of life is part of the economics. Mr. Newfield: I attended a conference for insurance companies and their attorneys where a doctor characterized CFS and FM as being either a somatoform disorder or merely psychological. If this gains any momentum, it could be disastrous to the community. Dr. Reeves: CFS is a mind/body illness. You can't separate them. How can I deal with the perceptions? I do not have a diagnostic marker, but I can show you changes in cognitive functions that go to the frontal cortex and basal ganglia. I can show you reproducible changes. It needs to accumulate in the literature. Mr. Newfield: My concern is that bundling these disorders would have a great effect on the population that suffers by giving the insurance companies a hook to say that this is a mental and nervous disorder to limit the period of disability pay. What is the CDC's position on bundling vs. bifurcating these conditions? Dr. Reeves: We really don't have one right now. We're going to go directly off of the evidence. The insurance companies are interested in bottom line. If the bottom line is that treating and appropriately diagnosing these conditions costs them less money, they're going to do it. Much of this involves the economics. We have not really done a lot with the HMOs and insurance companies yet. We're going to bring that in as part of the pilot registry, and we hope that we can change their approach based on knowledge. Mr. Newfield: My concern is that by and large the insurance companies that handle the healthcare aspects are, generally speaking, different that the ones that handle the compensation and disability issues. Aetna and Cigna do both, but by and large they are going to have different agendas. The healthcare company is going to want less money paid out for the healthcare costs, while the companies that do disability don't want to recognize the disability condition, so they're not necessarily coming to the table with the same approach. Dr. Joanne Cono Over the past two years, the CDC has been undergoing a structural reorganization. The CFS research program at CDC was formerly within the National Center for Infectious Diseases in the Division of Viral and Rickettsial Diseases. Under the reorganization, the three national centers that handled infectious disease entities-the National Immunization Program, the National Center for Infectious Diseases, and the National Center for HIV/AIDS, STD, and TB Prevention-were brought together under a Coordinating Center for Infectious Diseases and into four national centers: The National Center for Immunization and Respiratory Diseases With various programs being evaluated and realigned, it was a good juncture to look at the CFS program and where in the new structure the work could be supported. CDC embarked on a two-step review process of the program:
The group developed a final composite report, which is now with the CDC leadership for consideration about the future placement and research agenda of the program. Committee Q&A Dr. Jason: How will decreased funding for CDC impact the type of work that's going on at the CDC in this area? Dr. Cono: I don't have any additional information other that what Dr. Reeves shared earlier. My understanding is that FY 2007 funding has been level and the future is an unknown. Dr. Reeves: There are two issues. One is allocated funding and the other is payback funding, which went on the top of that. The allocated funding was approximately $4 million in 1998. Allocated funding was between $4 and $5 million in 1999. In 2000 it was a bit more; in 2002, allocated funding was approximately $6 million. Allocated funding has fallen since then to about the 1997 level. Payback was finished in 2005. It came about when a problem occurred in using the monies allocated by Congress for CFS. CDC recognized the mistake and restored the CFS funding that was inappropriately accounted for. Total payback was $12.9 million over five years. During that time, the program was funded at $8 million a year, a level that cannot be sustained with allocated funding alone. The total CDC budget in 2005 was a little over $8 million. Our current allocation in 2007 is $4.3 million to the CFS program. Dr. Oleske: The work that you said is still to be done in Georgia-is that going to be able to be funded at the $4 million level? Dr. Reeves: We initiated the contracts for the studies that we are currently doing in the last year of payback funding, so that the first follow-up in Georgia, the provider registry, and the in-patient clinical study were paid for from payback funds. Those funds no longer exist. We can complete the studies that I listed, but there will be insubstantial money to do anything like that in the future. Dr. Parekh: If the money stays the same, how much epidemiological work will be able to be done? Dr. Reeves: New field work (surveying populations and following them up)-none. Analysis, interpretation, working up the data-lots. But the problem becomes that the momentum stops. At the bottom line, we have lots of analysis and interpretation-several years worth of that-but as far as doing anything with it after that…once process stops, you do not just start it again. Dr. Oleske: It appears that for a variety of reasons, we're not going to see funding for the next several years for centers of care for large numbers of CFS patients. I'm concerned that while it was nice that we had this payback, from the point of support for CFS research, we're talking about the budget being cut in half. Those wonderful services we heard about in Albany are clearly not going to be available to those with CFS despite the fact that most of us would argue that those services are what our patients need. I probably don't have the right audience to answer the question, but it seems to me that however you slice it, we're going to see about a half cut in the budget for CFS for the United States in the foreseeable future, and I think that's drastic given the nature and extent of this disease. Dr. Glaser: It would be interesting in the context of this discussion to find out the total number of CFS grants NIH funded over the last three years. Dr. Oleske: CFSAC invited representatives from the professional medical associations to give presentations. None of them felt that it was a priority to send a representative to this panel. I'm finding out that we're still where we were 10 years ago with the professional physicians' groups not believing in CFS and our allies at CDC and NIH cutting back drastically on funding. CFS patients and their families are going to be left out in the cold. Dr. Reeves: If I go to the Infectious Diseases Society of America or the Allergy Society, I get a standing room only audience. Those groups are particularly keen to have credible information on CFS, and we did not solicit the invitation. Dr. Oleske: I may be misspeaking, and I apologize for that, but I still sense that there is a disinterest-at least among my peers that I see-for CFS. Dr. Bateman: What is the future of provider education through the CDC? Dr. Reeves: This is the last year of the provider education contract. We will be competing and advertising a new contract and we have the funding to pay for at least one year of it. It will be a similar type modified by what we're learned. It has a strong CME component and emphasizes getting information into medical school curricula via grand rounds that primarily target family practice, because that appears to be the group most interested. We are also targeting nurse practitioners and PAs. CDC leadership has bought into this enthusiastically. The Coordinating Center for Infectious Diseases is quite interested. There are crosses between other coordinating centers such as those involved in violence and chronic diseases as well as the cross-centers Public Health Genomics Working Group. We also have strong ties with the Health Marketing Group. Mr. Newfield: Dr. Reeves, what will be the ultimate outcome of your body of work if you're compelled by budgetary constraints to stop the fieldwork? Dr. Reeves: The fieldwork to do a population survey costs about $3 million. An in-hospital survey costs $1.5-$2 million. A provider registry costs about $2 million. Basically, we will analyze the data that we have in detail. We'll have data and one year's worth of follow-up, so we'll have some idea what the clinical course is for one year, as well as incident cases and economic impact over a year. We will have a pilot one-year provider registry and we will have one GCRC (general clinical research center) study. Early analysis should lead to the next study. Once you lose the cohort that you have picked up in a population survey and several years lapse, you cannot go back to it. There will be a lot of analysis and a lot of publication, but the ability to follow up on those will not exist. Dr. Hartz: How much data do you have from the GCRC? Dr. Reeves: The GCRC hasn't started yet, but those studies will be completed. It will be 120 patients-60 CFS, 60 control. Update from CDC - The Public Awareness CampaignFred Fridinger, DrPH, CHES, Project Manager, CDC CFS Public Awareness Campaign, National Center for Health Marketing The CFIDS Association is the main contractor for the awareness campaign along with Fleishman-Hillard, and they have done an exemplary job. I will update CFSAC on what has occurred since the media launch on November 3, 2006 and where we're going over the next year or two. This is a funded campaign through September 2009. Major media outlets in broadcast, web, and print venues (NBC Nightly News, Fox News, CNN, US News and World Report) covered the campaign launch. We have seen an increase in media pickup since that launch. We released public service and print ads as well as ancillary materials such as the CFS toolkit for health professionals and a variety of other downloadable items. The toolkit has six fact sheets on evidence-based approaches for diagnosis and treatment and includes a sample brochure. Highlights that demonstrate the broad exposure of the PSA through April 2007:
There is an evaluation being conducted by Porter Novelli using a survey tool called Health Styles that will measure public awareness about CFS. A similar tool called Doc Styles will measure awareness among medical professions, especially among CFS providers. The survey items were included last summer and will be included this summer as well to measure any increase in CFS awareness. Future campaign activities
Our center is uniquely situated from a federal agency perspective in that we have staff with skills and expertise to deal in various communication and marketing efforts. We have roughly four divisions within the National Center for Health Marketing:
We are actively attempting to go trans-center from a communications marketing perspective. Every Center at CDC has a Director, and that person has an Associate Director for Communication. Under the reorganization, that Associate Director is now an employee of our center. In essence, they are our representatives within the various Centers, Institutes, and Offices. We are trying to create those bridges so that public awareness campaigns are more integrated in program content and in terms of communication and marketing possibilities. My own branch has just taken on a couple of new activities. Two of these are in public engagement and long-lead media. The public engagement is using innovative technologies to reach the public. These technologies include cell phones, YouTube, and other alternative ways to reach people beyond traditional communication technology. Out long-lead media activities include a Health, Media, and Society Program that works with the University of Southern California's Hollywood and Media Society Program as well as with program writers and producers to promote public health issues. I don't recall anything being done on CFS, but this is a tremendous opportunity to explore how film, media, and TV can get CFS into the public eye. Committee Q&A Dr. Oleske: Since the message is helpful to a lot of Americans and it's politically neutral, it would be nice if some of the candidates in the debates would bring up the importance of supporting CFS. Ms. Artman: The demographics tend to show that a large Hispanic community also has CFS. In looking at who this is being marketed to, I didn't notice anything that is Hispanic-oriented. Kim McCleary (CFIDS Association of America): We did not have funding in the original budget to develop Spanish-language materials, and so we did not create outlets for reaching the Hispanic audience because we didn't have materials to deliver that were going to be consistent with the rest of the campaign. Dr. Fridinger: We now have a group that provides multi-lingual services as well as some translation capacity in the Creative Services Division, so there is opportunity in the future to develop CFS materials. Ms. Healy: Is there any way to know how many hits on the CDC CFS website went to the toolkit for providers to get a sense of who was looking at the materials? Is there a way to know how the toolkits were impacted by the public service campaign? Dr. Fridinger: I think that the only way to obtain that information is to have an on-site survey, which I don't think was available. Ms. McCleary: The way that CDC.gov is set up, there are no cookies or any way to identify where hits are coming from other than the referring URL. You can see the number of downloads of campaign materials in the statistics that Fred has provided that relate to the toolkit, but we don't have the capacity to discern who is downloading it. Dr. Jason: It would be helpful to CFSAC as we try to get a handle on funding to get a breakdown of the different activities and the different funding amounts. A follow-up question-there's been a lot of discussion over the last year of what the name of this illness is, and I'm wondering whether you've given any consideration to the topic of the name-whether you use ME/CFS or some other name in terms of branding. Dr. Fridinger: That's an interesting question from a communications standpoint. Given that I've just become more aware of this area in the past few months, it would seem to me that given the relatively short history of CFS in the public consciousness, the simpler, the easier to remember. There are two issues here. One is that once something is imprinted like CFS, it's very hard to change from a public perspective. The other thing is that the shorter terms and message slogans are, the easier they are to identify. If you want to make modifications, I think it's going to be difficult, although if you're going to do it, do it early on. About the monetary-would it be something as simple as looking at these general activities and roughly how much is dedicated them? Dr. Jason: Certainly that would be helpful. It would be helpful to know these different streams and how much it all adds up to-it could be more or less than we think. Dr. Reeves: I just want to make a comment on the name. That is not a public health marketing issue; that is a scientific issue. I would like to point out that names are not just assigned willy nilly by HHS or CDC. There is not a published international case definition for CFS/ME. There was an internationally-accepted definition of CFS developed in 1994 that has more than a thousand references in the scientific literature. I am not aware of a published, internationally-used case definition for an illness called CFS/ME. Dr. Klimas: We have to be careful-as we are a national advisory committee-what implications our work has on the international community. CFS/ME is a widely used name for this illness in other countries-the preferred name in many countries. By us strongly sticking behind the "CFS" without any slashes, we are more or less forcing this name in the international community. The Canadians did put together an international group to develop a clinical case definition and published that, and it is widely used and readily accessible. My question to you is on a very different subject. Are there any copyright issues involved with downloading material from the public awareness website, including translating it into other languages? Is provider education in the public awareness budget or another budget? Dr. Reeves: The provider piece is in the research budget because we developed it first, but they are two quite separate budgets. They are tightly coordinated, because in driving providers to the CDC or CFIDS website, we hope to get them into the CME website. But the provider education, since it's much more technical in nature, is a program activity. Dr. Klimas: You are targeting physician extenders and family practitioners. Internal medicine doctors make up the vast majority of outpatient-based primary care. Why aren't we targeting them? Dr. Reeves: We've got a limited amount of money that we can spend. We try to spend it where we get the biggest bang for buck. With the new contract coming out, we will have the same fiscal constraints as we have now. We seem to have a bigger bang for our buck from grand rounds and presentations than we do for other things, although these others are very successful. Ground rounds are targeting family practice, nurse practitioners, and PAs. We do the others, but we're aiming at these. Dr. Klimas: I'd hope that you'd be able to widen that in some way, and if you can't, then maybe we can work with the Health Resources and Services Administration or someone else so that it can be done. This committee's charge is to come up with the bigger picture, and the bigger picture is that they all need to be trained. We need to make this model accessible to the bigger group. Ms. McCleary: Through the public awareness campaign, we have targeted medical media as well as lay media. As a result, there have been an increased number of CFS articles in the medical media-not the peer review literature, but the other publications that healthcare professionals read such as American Medical News and OBGYN News and a number of disciplines that are not being targeted by the provider education project specifically. Also, healthcare professionals read the New York Times and the Chicago Tribune and People magazine just like everybody else. Dr. Hartz: When you say you target one specialty, how do you decide which one, and would it make sense to have training institutions self-select which group is most interested? Dr. Reeves: It is difficult to get this into the curricula of medical schools. Ground rounds are great because they give access to people in training, they have both medical students and post-doctoral people, they have practicing physicians who are on the faculty, and other faculty. We have targeted those universities that have family practice because they have been particularly interested and there's a finite number. You can go multiple times. We always try to get the bang for the buck, and OFFER is a good example. Utah put on a special conference of continuing medical education two months earlier where I was invited as a keynote speaker, and it coincided with the OFFER conference. Dr. Bateman set up grand rounds with both internal medicine and family practice. The Mayo Clinic is a group that may now be interested in grand rounds. That would be a very good group to hit even though they're not family practice. We won't turn down anything, but as far as our targeting and our resources, that is who we're aiming at. Dr. Oleske brought up the humanism in medicine trend and pointed out that CFS can illustrate many of the issues around humanism. He suggested that CFSAC could take advantage of that trend to put forward the concept that CFS is a great model. Dr. Hartz: If you get the word out to more education institutions and it creates so much demand that you can't cover them all, you can ask how many and what types of people will be in the audience and direct your resources to the highest priority. Ms. McCleary: That is what we're doing. We actively solicit participation in grand round programs at a number of schools with family practice and other priority programs. But when we do get one booking, we try to expand it out to do programming at other schools and hospitals, including using technology for remote participation. Dr. Fridinger: The materials are appropriate for most medical specialties; it's just a matter of getting it to them through their dissemination and training channels. Dr. Papernik: Patients learn a lot about disease states from direct-to-consumer advertising and Oprah. Is there any pressure that you can exert to get Oprah to do a program on CFS? Ms. McCleary: She did a segment on June 24, 1998, on hard-to-diagnose diseases and CFS was included in that. Fleishman-Hillard has a relationship with her company. O magazine included a lengthy article last summer and we were hoping that would translate into an appearance on the show, but so far I don't have any date to report. Dr. John: In this groundswell that's taking place, we're going to produce what seems like a large number of new patients. This is a complex disease that cannot be taken care of easily by a primary care provider. Progressively, the more complex decisions in these cases must be made by physicians who focus on the disease. In a state like South Carolina, there are so few. In some states we don't have any named. We need to reach medical students in years one and two. It's OK to have grand rounds, but that's not a true curricular activity. Along with all your deliberations, I would recommend that we also concentrate on the ultimate development of a group of people to better take care of this complex group of patients. Mr. Newfield: A North Carolina mother with a child with CFS recently approached me because she was unable to get care. The state Center for Health Statistics, Division of Public Health, wrote her back asking her to explain the acronyms "CFIDS" and "CFS", so they don't know the acronyms. Public awareness needs to be aimed also towards governmental agencies charged with public health. [Dr. Oleske called a five minute break.] Ex-Officio UpdatesDr. Marc Cavaille-Coll, FDA The accompanying document includes background information provided at previous CFSAC meetings as well as contact information and other resources. Some highlights include:
Committee Member Q&A Dr. Papernik: Does FDA go through the same process for approving the new use of a drug that has already been approved for another illness? Dr. Cavaille-Coll: Any company that has a lawfully marketed product for which it wants to develop a new indication is free to conduct a development program and clinical trials, then submit a supplementary new drug application or efficacy supplement with adequate, well-controlled trials, and we will review that. That's something that needs to be initiated by the companies if they want to do that. Dr. Papernik: So they're subject to the same rigorous criteria as if they were bringing the drug before the FDA for the first time? Dr. Cavaille-Coll: It's the same for every indication. The statutes say that there has to be substantial evidence of efficacy and safety as demonstrated by adequate, well-controlled trials. It's the same standard. There are other standards that have to do with manufacturing, potency purity, and toxicology which hopefully have been solved by then. A lot of the clinical pharmacology questions have already been answered, so the am |